Re-evaluation of HER2 status in 606 breast cancers—gene protein assay on tissue microarrays versus routine pathological assessment

Sandén, Emma; Khazaei, Sedigheh; Tryggvadottir, Helga; Borgquist, Signe; Isaksson, Karolin; Jirström, Karin; Jernström, Helena

doi:10.1007/s00428-020-02768-x

Cited by 13 publications

(13 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If the pathology reports lacked data on human epidermal growth factor receptor 2 (HER2) amplification, HER2 status was obtained from dual gene protein staining of HER2 on TMAs from the patients’ tumors. This method showed an agreement of 97.7% with available pathological assessment ( 24 ). The patients were followed up until June 30, 2019.…”

Section: Methodsmentioning

confidence: 59%

Prognostic impact of tumor-specific insulin-like growth factor binding protein 7 (IGFBP7) levels in breast cancer: a prospective cohort study

et al. 2021

Self Cite

View full text Add to dashboard Cite

The prognostic impact of insulin-like growth factor binding protein 7 (IGFBP7) in breast cancer is unclear. Host factors, including lifestyle, anthropometry, and metabolic profile, might influence tumor-specific IGFBP7. This study aimed to investigate whether IGFBP7 levels and mRNA expression are associated with the patient and tumor characteristics and prognosis in breast cancer. Patients with primary breast cancer in Lund, Sweden, were included preoperatively in the study between 2002 and 2012 (n = 1018). Tumor-specific IGFBP7 protein levels were evaluated with immunohistochemistry using tissue microarrays in tumors from 878 patients. IGFBP7 mRNA expression and its corresponding clinical data were obtained from The Cancer Genome Atlas (TCGA) and analyzed for 809 patients. Tumor-specific IGFBP7 protein levels were categorized based on Histo 300 scores into IGFBP7low (6.2%), IGFBP7intermediate (75.7%), and IGFBP7high (18.1%). Both low IGFBP7 protein levels and mRNA expression were associated with less aggressive tumor characteristics. Overall, IGFBP7low conferred low recurrence risk. The prognostic impact of IGFBP7high varied according to any alcohol consumption and tamoxifen treatment. IGFBP7high was associated with low recurrence risk in alcohol consumers but high recurrence risk in alcohol abstainers (Pinteraction= 0.039). Moreover, the combination of IGFBP7high and estrogen receptor-positive tumors was associated with low recurrence risk only in tamoxifen-treated patients (Pinteraction= 0.029). To conclude, IGFBP7low might be a good, independent prognosticator in breast cancer. The prognostic impact of IGFBP7high depends on host factors and treatment. IGFBP7 merits further investigation to confirm whether it could be a suitable biomarker for treatment selection.

show abstract

Section: Methodsmentioning

confidence: 59%

Prognostic impact of tumor-specific insulin-like growth factor binding protein 7 (IGFBP7) levels in breast cancer: a prospective cohort study

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Prognostic associations for AhR became stronger when HER2 was included in the multivariable models (data not shown). However, HER2 status was more often missing from small tumors with longer follow-up times ( 36 ) and inclusion of this marker could bias the analyses. Therefore, HER2 status was not used in the multivariable analyses presented.…”

Section: Discussionmentioning

confidence: 99%

“…HER2 status (amplified/non-amplified) was incorporated into a clinical routine in November 2005 and was available for most tumors after that date. Clinical HER2 status was supplemented with retrospective HER2 analysis by gene protein assay on tissue microarrays (TMA) ( 36 ). Information on histological type and grade, invasive tumor size, and axillary node involvement (ALNI) was retrieved from the patient charts and pathology reports.…”

Section: Methodsmentioning

confidence: 99%

The Prognostic Impact of Intratumoral Aryl Hydrocarbon Receptor in Primary Breast Cancer Depends on the Type of Endocrine Therapy: A Population-Based Cohort Study

et al. 2021

Self Cite

View full text Add to dashboard Cite

The aryl hydrocarbon receptor (AhR) is a master regulator of multiple pathways involved in breast cancer, and influences the estrogen receptor alpha (ER) and aromatase/CYP19A1. The purpose of this study was to elucidate the interplay between intratumoral levels of AhR and aromatase, patient characteristics (including AhR and CYP19A1 genotypes), clinicopathological features, and prognosis in breast cancer patients receiving adjuvant treatments. A prospective cohort of 1116 patients with primary breast cancer in Sweden, included 2002–2012, was followed until June 30th 2019 (median 8.7 years). Tumor‐specific AhR (n=920) and aromatase levels (n=816) were evaluated on tissue microarrays using immunohistochemistry. Associations between cytoplasmatic (AhRcyt) and nuclear (AhRnuc) AhR levels, intratumoral aromatase, clinicopathological features, and prognosis in different treatment groups were analyzed. Low AhRcyt levels (n=183) and positive intratumoral aromatase (n=69) were associated with estrogen receptor (ER)– status and more aggressive tumors. Genotypes were not associated with their respective protein levels. The functional AhRArg554Lys GG genotype was associated with recurrence-free survival in switch-therapy (sequential tamoxifen/aromatase inhibitors (AI) or AI/tamoxifen) treated patients (HRadj 0.42; 95% CI 0.22–0.83). High AhRcyt levels were associated with longer recurrence-free survival during the first 10 years of follow-up among tamoxifen-only treated patients (HRadj 0.40; 95% CI 0.23–0.71) compared to low AhRcyt levels, whereas an almost inverse association was seen in patients with switch-therapy (Pinteraction=0.023). Intratumoral aromatase had little prognostic impact. These findings warrant confirmation in an independent cohort, preferably in a randomized clinical trial comparing different endocrine regimens. They might also guide the selection of breast cancer patients for clinical trials with selective AhR modulators.

show abstract

“…Clinical HER2 status was supplemented with HER2 status obtained by retrospective HER2 analysis with gene protein assay using tissue microarrays (TMA) for 269 patients. The agreement in HER2 status between the pathological assessment using whole slides and TMA was 97.7% ( 28 ).…”

Section: Methodsmentioning

confidence: 99%

Patient Characteristics Influence Activated Signal Transducer and Activator of Transcription 3 (STAT3) Levels in Primary Breast Cancer—Impact on Prognosis

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background: Activated signal transducer and activator of transcription 3 (pSTAT3) is often present in breast cancer, but its prognostic impact is still unclear. We investigated how breast tumor-specific pSTAT3 Y705 levels are associated with patient and tumor characteristics and risk of recurrence. Materials and Methods: Primary breast cancer patients without preoperative treatment were included preoperatively. The patients were treated in Lund, Sweden, in 2002–2012 and followed until 2016. Levels of pSTAT3 Y705 were evaluated in 867 tumors using tissue microarrays with immunohistochemistry and categorized according to the H-score as negative (0–9; 24.2%), intermediate (10–150; 69.9%), and high (160–300; 5.9%). Results: Patients were followed for up to 13 years, and 137 recurrences (88 distant) were recorded. Higher pSTAT3 Y705 levels were associated with patient characteristics including younger age, any alcohol consumption, higher age at first child birth, and smaller body size, as well as tumor characteristics including smaller tumor size, lower histological grade, lymph node negativity, progesterone receptor positivity, and HER2 negativity (all P trends ≤ 0.04). Higher pSTAT3 Y705 levels were associated with lower risk of early recurrences (LogRank P trend = 0.10; 5-year LogRank P trend = 0.004) and distant metastases (LogRank P trend = 0.045; 5-year LogRank P trend = 0.0007), but this was not significant in the multivariable models. There was significant effect modification between tamoxifen treatment and pSTAT3 Y705 negativity on the recurrence risk in chemonaïve patients with estrogen receptor positive tumors [adjusted hazard ratio (HR) 0.38; P interaction = 0.046]. Conclusion: Higher pSTAT3 Y705 levels were associated with several patient and tumor characteristics that are mainly associated with good prognosis and a tendency toward lower risk for early recurrences. In the future, these results may help guide the selection of patients for trials with drugs targeting the STAT3 pathway.

show abstract

Re-evaluation of HER2 status in 606 breast cancers—gene protein assay on tissue microarrays versus routine pathological assessment

Cited by 13 publications

References 14 publications

Prognostic impact of tumor-specific insulin-like growth factor binding protein 7 (IGFBP7) levels in breast cancer: a prospective cohort study

Prognostic impact of tumor-specific insulin-like growth factor binding protein 7 (IGFBP7) levels in breast cancer: a prospective cohort study

The Prognostic Impact of Intratumoral Aryl Hydrocarbon Receptor in Primary Breast Cancer Depends on the Type of Endocrine Therapy: A Population-Based Cohort Study

Patient Characteristics Influence Activated Signal Transducer and Activator of Transcription 3 (STAT3) Levels in Primary Breast Cancer—Impact on Prognosis

Contact Info

Product

Resources

About